The goal of this project is to increase our understanding of the terminal steps in megakaryocyte development. We will isolate subpopulations of megakaryocytes and subject them to electron microscopic, cytochemical and functional analysis. Megakaryocyte ploidy values will be correlated with the development of cellular organelles. The influence of thrombopoetin, erythropoietin and megakaryocyte colony stimulating activity on megakaryocyte organelle development will be assessed. Megakaryocyte organelle maturity and nuclear differentiation will be simultaneously assessed. Ultrastructural abnormalities of megakaryocytes obtained from patients with congenital and acquired disorders affecting platelets will be examined. The study of congenital and acquired qualitative platelet disorders will allow us to translate abnormalities in megakaryocyte development into resultant functional and ultrastructural defects in platelets.